Major Research Findings

Efavirenz (EFV) is an antiretroviral drug used to treat HIV, but it is known to cause neuropsychiatric side effects and an unfavorable blood lipid profile. Several studies have investigated the effects of replacing EFV with etravirine (ETR) on patient preference, sleep, anxiety, and lipid levels.

2 conducted a randomized crossover trial comparing EFV and ETR treatment. The study found that patient preference for treatment was significantly influenced by the order in which the drugs were taken. 71% of patients who continued on EFV during the first phase of the trial preferred EFV, while 94% of patients who started with ETR preferred ETR. However, when considering overall treatment preference after 12 weeks, 16 preferred EFV, 22 preferred ETR, and 17 did not express a preference (P = NS). There was no significant difference between groups in sleep quality, depression, anxiety, or stress scores. Median plasma cholesterol levels decreased by 0.7 mmol (29 mg/100 ml) after replacing EFV with ETR (P < 0.002).

1 conducted a long-term study tracking the neuropsychological performance of HIV-infected individuals on EFV-based regimens for over 3 years. The study found that neuropsychological performance improved from baseline in patients who continued on EFV-based regimens and was maintained over 3 years. While EFV-associated CNS symptoms increased slightly, overall symptom scores did not change. Median change of bad dream sleep scores and anxiety increased from baseline while global depression score decreased.

3 conducted a systematic review to determine if there is evidence that efavirenz may contribute to cognitive impairment by damaging nerve cells. The study found limited clinical evidence suggesting that efavirenz use may worsen neurocognitive impairment or be associated with less improvement in neurocognitive impairment than other antiretrovirals. However, they discovered that efavirenz, especially its major metabolite 8-hydroxy-efavirenz, is toxic to neuron cultures at concentrations found in the cerebrospinal fluid. This suggests that individuals who are extensive metabolizers of efavirenz may be more likely to experience efavirenz toxicity due to the formation of more 8-hydroxy-efavirenz.

6 compared the differential effects of first-line efavirenz (EFV)-based vs. boosted lopinavir-based antiretroviral regimens on cholesterol metabolism. They found that treatment with a ritonavir-boosted lopinavir (LPV/r)-based therapy increased total cholesterol relative to EFV-based therapy. Their data suggests that absorption rather than synthesis is the mechanism involved in LPV/r-associated increased total cholesterol.

4 compared the pharmacokinetics and pharmacodynamics of once-daily efavirenz (400 mg vs. 600 mg) in treatment-naïve HIV-infected patients. They found that EFV 400 mg was virologically noninferior to EFV 600 mg at 48 weeks. However, EFV 400 mg exposure was significantly lower compared to EFV 600 mg. EFV exposure was associated with several factors, including patient demographics and genetic polymorphisms. Despite significantly lower EFV400 exposure, HIV suppression was comparable between doses. The study also revealed important limitations in the accepted threshold concentration for efavirenz.

7 assessed the effect on cognition of switching Atripla (TDF/FTC/EFV) to Eviplera (TDF/FTC/RPV) in asymptomatic patients, hypothesizing an improvement when discontinuing efavirenz. The study suggested that discontinuing efavirenz may improve cognitive function objectively and subjectively.

5 investigated the efficacy and safety of valerian in preventing neuropsychiatric adverse effects of efavirenz in HIV-positive patients. The study found that valerian significantly improved sleep and anxiety compared to placebo. However, the study was small and further investigation is warranted.

Benefits and Risks

Benefit Summary

Replacing EFV with ETR may lower cholesterol levels and potentially reduce neuropsychiatric side effects.

Risk Summary

Replacing EFV with ETR may alter patient preference for treatment and potentially decrease viral suppression if EFV levels fall too low.

Study Comparisons

Study Commonalities

Multiple studies indicate that EFV can influence neuropsychiatric side effects and blood lipid profiles. Studies also suggest that replacing EFV with other antiretrovirals may reduce these side effects.

Study Differences

Studies differ in the replacement drug used, the patient populations studied, and the specific outcomes assessed. For example, 2 explored patient preference after replacing EFV with ETR, while 1 examined the long-term neuropsychological performance of patients on EFV-based regimens.

Consistency and Contradictions in Results

Multiple studies have demonstrated that EFV can influence neuropsychiatric side effects and blood lipid profiles. However, the results regarding patient preference for treatment and viral suppression after replacing EFV with other antiretrovirals are inconsistent. This inconsistency may be due to differences in the study populations and methods.

Practical Application Considerations

Replacing EFV with other antiretrovirals should be a personalized decision based on individual patient needs and preferences. Close communication with a physician is crucial to determine the best treatment approach for each patient.

Limitations of Current Research

Many studies are limited by small sample sizes and require further investigation. There is also much that is still unknown about the long-term effects of EFV and its interactions with other antiretroviral medications.

Future Research Directions

Further research is needed to assess the long-term effects and side effects of replacing EFV with other antiretrovirals and to examine the impact on patient quality of life. Research into the metabolism and pharmacokinetics of EFV is also important.

Conclusion

While EFV is an effective treatment for HIV, it is known to cause neuropsychiatric side effects and unfavorable blood lipid profiles. Replacing EFV with other antiretrovirals is being investigated as a means of reducing these side effects. However, the decision to replace EFV should be personalized and based on individual patient needs and preferences. Close communication with a physician is crucial to determine the best treatment approach.